ASRA Updates

Patient Selection for Peripheral Nerve Stimulation

Feb 6, 2021

Nathan J. Harrison, MD
neuromodulation peripheral nerve stimulation

By Nathan J. Harrison, MD
Senior Physician, Interventional Pain Management
Department of Anesthesiology and Critical Care Medicine
Ochsner Health System
New Orleans, LA


Background

Electrical stimulation of a peripheral nerve was first performed in 1859 by Julius Althaus in order to alleviate surgical pain in an extremity. In 1965, Wall and Sweet studied percutaneous sensory nerve stimulation and found paresthesia could be produced. The first application of peripheral nerve stimulation (PNS) with implantation involved invasive surgical dissection to allow placement of a paddle electrode lead in close proximity to the targeted nerve. However, this could result in significant post-operative pain and scarring, making revisions difficult. Newer techniques involve percutaneous placement of the electrode lead under ultrasound guidance which allows a less invasive approach to superficial but also deeper targets. A drawback to a PNS, however, is placement of the internal pulse generator; especially when a target nerve is in a distal extremity, lengthy tunneling to a body site to provide ample space for the generator is required. Recent innovations include external pulse generators that can be worn close to or affixed to the body site over the implanted lead. Finally, while the advent of dorsal root ganglion stimulation has brought about success in treating some more focal pain syndromes involving CRPS, PNS remains relevant in treating mononeuropathies.

Mechanism of Action

The gate control theory introduced by Wall and Melzack in 1965 suggests that low intensity peripheral nerve stimulation preferentially activates the large A sensory fibers, thereby disrupting nociceptive input from the smaller C-fibers.  While this theory helped develop our initial understanding of the mechanism of action for PNS, further study has revealed that PNS likely works both through a peripheral and central mechanism. In terms of the peripheral mechanism, research on electroacupuncture has shown activation of the sympathetic nervous system with resulting endogenous opioid release from adrenergic receptors and fibroblasts, upregulation of the cannabinoid CB2 receptors and inhibition of COX. Similarly, research on transcutaneous electrical nerve stimulation (TENS) at low amplitude shows stimulation of the A sensory fibers for a gate theory type effect; at high intensity, TENS stimulated the A fibers which then induced  endogenous opioid expression and depressed nociceptive pathways via the -opioid, serotonin, GABA, and muscarinic receptors. Animal studies of PNS effects on the central nervous system reveal increased inhibition of the dorsal wide dynamic range neurons at the spinal level where they interact with nociceptive fibers, allowing improved endogenous pain inhibition. In positron emission tomography studies, PNS increased cerebral blood flow to the primary somatosensory cortex, anterior cingulate, and the thalamus suggesting possible supraspinal mechanism. Although many PNS studies have been conducted over the last several decades, the mechanism of action is still poorly understood.

Current and Future Uses

Treating craniofacial pain remains one of the more common uses of PNS as dorsal column and dorsal root ganglion stimulation typically cannot address this pain. Stimulation of the infraorbital and supraorbital nerves has successfully treated pain from postherpetic neuralgia and trigeminal posttraumatic neuropathic pain. Occipital neuralgia, chronic migraines, and cluster headaches can respond to placement of leads in the region of the occipital nerves. Amputee and phantom limb pain can be difficult to treat well with traditional SCS and recent studies show promise in these pain syndromes. Peripheral nerve field stimulation (PNfs) consists of placing one or more leads that may cross overlapping fields of multiple nerves. PNfs can be used alone or in hybrid with SCS to treat truncal or axial neck and back pain, chest, and abdominal wall pain. Traditionally, PNS use has been targeted at neuropathic pain as previously mentioned. However, several more recent studies have explored PNS use in a more nociceptive pain environment of knee and rotator cuff postoperative management.

While most PNS usage consists of adapting spinal cord stimulator electrode leads and placing these in proximity to a peripheral nerve, most uses are considered off-label. Recently, the US Food and Drug Administration approved single- and dual-lead PNS systems for the treatment of chronic and acute pain, including post-traumatic and postoperative pain, for up to 60 days. Two feasibility studies recently evaluated the use of this PNS system for postoperative pain control: one in total knee arthroplasty with stimulation of the femoral and sciatic nerve, and the other in rotator cuff repair by stimulating the suprascapular nerve and brachial plexus. Both of these studies demonstrated encouraging results for pain relief; however, larger studies are needed.

Other nerves currently under study for possible benefit for PNS include saphenous and geniculate nerves for chronic knee pain, axillary and suprascapular nerve for chronic shoulder, articular branches of the femoral and obturator nerves for chronic groin and hip pain, superior gluteal nerve for greater trochanteric pain, and cluneal nerves for back pain. 

Patient Selection

In 2014, The Neuromodulation Appropriateness Consensus Committee evaluated the evidence regarding spinal cord and peripheral nerve neurostimulation and provided recommendations for usage of PNS. They provided two specific recommendations:

  1.  “The use of PNS should be reserved for patients in whom the pain distribution is primarily in and in close proximity to a named nerve known to innervate the area of pain.”
  2.  “With PNS or peripheral nerve field stimulation, temporary relief of the patient’s pain by an injection of local anesthetic in the nerve distribution should be seen as an encouraging sign, but not mandatory, as prognostic value is not established.”

Prior to considering PNS, conservative treatments should be exhausted, including medication trials and various pain management strategies such as injections, physical therapy, and other non-invasive treatments. As recommended by NACC, the decision to use PNS should be made based not only on location of pain, but also the knowledge of a specific nerve that innervates the location. If this nerve can be reasonably accessed with ultrasound or surgical dissection and an electrode lead or paddle can be placed along a section of the nerve, a trial can be considered. A diagnostic nerve block can be performed prior to a trial but as stated by NACC, successful pain relief with the block will not ensure that PNS will provide success, nor does failure of a diagnostic block necessarily predict future failure of a PNS trial.

As with spinal cord stimulation (SCS) for painful syndromes, PNS candidates should undergo psychological testing to address any psychiatric comorbidities and optimize management of depression that may impact pain coping. Preoperative planning should also include assessment of dermatological/infection status of the region of interest, laboratory testing to ensure adequate platelet counts, and optimization of other health issue such as diabetes that can place the patient at risk for poor wound healing and infection.

Once a patient has been identified as a candidate for PNS, a trial should be performed to evaluate whether the therapy is successful. NACC recommends that, “a successful trial should be defined as the patient having had at least 50% pain relief; evidence of improved function is a goal and should be measured in appropriate patients.”

Conclusion

Advances in peripheral nerve stimulation technology such as smaller devices and less invasive implanting techniques have led to the possibility of further uses of this neuromodulation treatment. Aside from traditional uses for treating chronic neuropathic pain syndromes such as with a mononeuropathy, there have been promising developments in treating nociceptive postoperative pain. While a great deal of excitement surrounds the future of PNS, the dearth of clinical studies leaves us without evidence-based data to support all of its possible uses. Nonetheless, continued studies to better understand mechanism of action and larger long term studies will hopefully provide better insight to the future this neuromodulation technology.

Bibliography

Chakravarthy K, Nava A, Christo PJ, Williams K. Review of Recent Advances in Peripheral Nerve Stimulation (PNS). Curr Pain Headache Rep. 2016;20(11):60.

Deer TR, Mekhail N, Provenzano D, et al. The Appropriate Use of Neurostimulation of the Spinal Cord and Peripheral Nervous System for the Treatment of Chronic Pain and Ischemic Diseases: The Neuromodulation Appropriateness Consensus Committee. Neuromodulation. 2014;17(6):515-550.

Banks GP, Winfree CJ. Evolving Techniques and Indications in Peripheral Nerve Stimulation for Pain. Neurosurg Clin N Am. 2019;30(2):265-273.

Goroszeniuk T, Pang D. Peripheral Neuromodulation: A Review. Curr Pain Headache Rep. 2014 May;18(5):412. 

Sivanesan E, Gulati A. Resurgence of Peripheral Nerve Stimulation With Innovation in Device Technologies. Reg Anesth Pain Med. 2019;44(6):615-616.

Lin T, Gargya A, Singh H, Sivanesan E, Gulati A. Mechanism of Peripheral Nerve Stimulation in Chronic Pain. Pain Medicine. 2020;21(S1):S6-S12.

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